Immune System Cells

Below is a graphic to help understand the basic components of the immune system. The first cell (the green stem cell) is in the bone marrow. It can become either a lymphoid stem cell (blue) or a myeloid progenitor (yellow).

Innate Immune System

The first line of the first line of defense against bacteria and other microorganisms is the innate immune system. The myeloid progenitors create the innate immune system, made up of a group of cells called granulocytes. Once a foreign substance enters the body, cells of the innate immune system work to remove that substance, recruit other cells to the area by releasing cytokines, and activate the adaptive immune system.

Adaptive Immune System

The adaptive immune system spring from the lymphoid stem cells. Lymphocytes evolve either in the bone marrow–called B-cells–or in the thymus–called T-cells.

The innate immune system is important in instigating and directing the adaptive immune cells responses. Dendritic cells and macrophages are the links between the innate and adaptive immune system.

Immature dendritic cells are found in all tissues and their purpose is to sample their environment for foreign substances or antigens. When they connect with those substances, they quickly mature becoming Antigen Presenting Cells (APCs). They then go to the lymph nodes where they activate T-cells and B-cells.

T-cells become T-helper (Th) cells and cytotoxic (Tc) T-cells. Cytotoxic means that it kills cells that are damaged. When B-cells are presented with an antigen, they change into a plasma cells and creates antibodies to the antigen.

Much research has been done on activating the adaptive immune system to seek out cancer cells. Here are a few of the strategies being used.

Monoclonal Antibodies

Antibodies (like those produced by B-cells) can be designed in the lab to target antigens that are found on cancer cells. These are called monoclonal antibodies. Trastuzumab (Herceptin®) is an example of a monoclonal antibody used to treat breast cancer. Below is a video by the Cancer Research Institute describing monoclonal antibodies.

One of the jobs of the T-cells is to check proteins on the surfaces of cells to determine if the cell is normal. If the cell is infected or cancerous, the T-cell destroys it. To stop T-cells from destroying them, cancer cells produce a protein called PDL-1, an immune checkpoint molecule that stops T-cells from destroying it. Researchers have fashioned antibodies, called checkpoint inhibitors, to intervene in this process. Ipilimumab (Yervoy), Nivolumab (Opdivo) and Pembrolizumab (Keytruda) are examples of these drugs.
Below is a video by Dana Farber Cancer Institute to describe checkpoint inhibitors.

Adoptive Cell Therapy

Researchers have found that there are lymphocytes in tumors that are trying to fight the cancer called tumor-infiltrating lymphocytes or TILs. In this immunotherapy strategy, these TILs are harvested from the person’s tumors and tested to see which are the most effective in killing the cancer cells. Those are grown in the lab and then put back into the patient.

To prepare the patient for the infusion of so many TILs, the patient has to go through high dose chemotherapy for lymphodepletion.

After the re-engineering, the CAR T-cells are grown in the lab and once millions have grown the patient receives them in an infusion. They grow in the body and attack the cancer cells. These cells remain circulating in the body and help to guard against cancer recurrence.

Here is a video by the Cancer Research Institute describing ACT.

Oncolytic Viruses

This strategy involves genetically modifying viruses so that they kill cancer cells. The virus is injected into the cancer; it does not enter healthy cells. It starts to make copies of itself and causes the cancer cells to explode. Antigens are released into the surrounding tissue which are taken up by immature dendritic cells and activate T-cells and B-cells to target cancer cells. T-VEC (talimogene laherparepvec–Imlygic) is the name of the first oncolytic treatment. Here is a video from Cold Genesys.

It is safe to say that, in the 45 years since this interaction, enormous progress has been made in understanding cancer: how it starts and what happens in cancer cells and the immune system.

In the abstracts presented at ASCO 2016, the huge advances in molecular biology, microbiology and computer capacity are making a difference. Who could have imagined in 1971 that it would be possible for scientists to engineer molecules to attach to T-cells that specifically target cancer cells? And that, with this one treatment strategy, people who had metastatic cancer are now surviving with “durable complete regression” of their cancer.